Abstract
The comparison of genotype frequencies between neonates and elderly populations can aid in the identification of loci, and polymorphisms within those loci, that affect longevity. Here we have compared genotype frequencies of seven polymorphisms at four loci involved in DNA repair between a cohort of newborns (n = 290) and a retired population (average age at sampling 70.02 years; n = 430) who have suffered a lifetime of DNA damage from normal, metabolic processes, and on whom selection on DNA repair gene variants may be expected to have acted. No differences in genotype frequencies at the four SNP loci were seen, indicating that there is no evidence of association with longevity in this population. Significant differences in frequency of certain repeat sizes at three microsatellite loci were detected. However, since there is no known functional consequence of these repeat lengths, the action of selection cannot yet be ascribed.
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References
M Akiyama S Kyoizumi Y Hirai Y Kusunoki KS Iwamoto N Nakamura (1995) ArticleTitleMutation frequency in human blood cells increases with age Mutat Res 338 141–149 Occurrence Handle1:CAS:528:DyaK2MXotFCrtb0%3D Occurrence Handle7565869
J Baillargeon (2001) ArticleTitleCharacteristics of the healthy worker effect Occup Med 16 359–366 Occurrence Handle1:STN:280:DC%2BD3M3jtVOjug%3D%3D Occurrence Handle11319057
YA Barnett CM King (1995) ArticleTitleAn investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans Mutat Res 338 115–128 Occurrence Handle1:CAS:528:DyaK2MXotFCrtb8%3D Occurrence Handle7565867
B Bessenyei M Marka L Urban M Zeher I Semsei (2004) ArticleTitleSingle nucleotide polymorphisms: aging and diseases Biogerontology 5 291–303 Occurrence Handle10.1007/s10522-004-2567-y Occurrence Handle1:CAS:528:DC%2BD2cXpvVers70%3D Occurrence Handle15547317
VA Bohr (2002) ArticleTitleRepair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells Free Radic Biol Med 32 804–812 Occurrence Handle10.1016/S0891-5849(02)00787-6 Occurrence Handle1:CAS:528:DC%2BD38XjtVeju70%3D Occurrence Handle11978482
PC Burcham (1999) ArticleTitleInternal hazards: baseline DNA damage by endogenous products of normal metabolism Mutat Res 443 11–36 Occurrence Handle1:CAS:528:DyaK1MXls1Olt7g%3D Occurrence Handle10415429
DS Chase EJ Tawn L Parker P Jonas CO Parker J Burn (1998) ArticleTitleThe North Cumbria Community Genetics Project J Med Genet 35 413–416 Occurrence Handle1:STN:280:DyaK1c3nt1egtQ%3D%3D Occurrence Handle9610806
PF Chinnery DC Samuels J Elson DM Turnbull (2002) ArticleTitleAccumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? Lancet 360 1323–1325 Occurrence Handle10.1016/S0140-6736(02)11310-9 Occurrence Handle1:CAS:528:DC%2BD38XotFyqtLw%3D Occurrence Handle12414225
L Christiansen HC Petersen L Bathum H Frederiksen M McGue K Christensen (2004) ArticleTitleThe catalase -262C/T promoter polymorphism and aging phenotypes J Gerontol 59A 886–889 Occurrence Handle1:CAS:528:DC%2BD2cXpslGhsLo%3D
F Cottet H Blanche P Verasdonck I Gall ParticleLe F Schachter A Burkle ML Muiras (2000) ArticleTitleNew polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity J Mol Med 78 431–440 Occurrence Handle10.1007/s001090050488 Occurrence Handle1:CAS:528:DC%2BD3cXos12jtbw%3D Occurrence Handle11097112
G Benedictis ParticleDe L Carotenuto G Carrieri M Luca ParticleDe E Falcone G Rose S Cavalcanti F Corsonello E Feraco G Baggio S Bertolini D Mari R Mattace AI Yashin M Bonafe C Franceschi (1998) ArticleTitleGene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2) Eur J Hum Genet 6 534–541 Occurrence Handle9887369
G Benedictis ParticleDe Q Tan B Jeune K Christensen SV Ukraintseva M Bonafe C Franceschi JW Vaupel AI Yashin (2001) ArticleTitleRecent advances in human gene-longevity association studies Mech Ageing Dev 122 909–920 Occurrence Handle11348658
EL Goode CM Ulrich JD Potter (2002) ArticleTitlePolymorphisms in DNA repair genes and associations with cancer risk Cancer Epidemiol Biomarkers Prev 11 1513–1530 Occurrence Handle1:CAS:528:DC%2BD3sXmsF2msA%3D%3D Occurrence Handle12496039
P Hasty (2005) ArticleTitleThe impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice Mech Ageing Dev 126 71–77 Occurrence Handle10.1016/j.mad.2004.09.036 Occurrence Handle1:CAS:528:DC%2BD2cXhtVyqs73L Occurrence Handle15610764
P Hasty J Campisi J Hoeijmakers H Steeg Particlevan J Vijg (2003) ArticleTitleAging and genome maintenance: lessons from the mouse? Science 299 1355–1359 Occurrence Handle10.1126/science.1079161 Occurrence Handle1:CAS:528:DC%2BD3sXhsFWrsL0%3D Occurrence Handle12610296
Y Hochberg (1988) ArticleTitleA sharper Bonferroni procedure for multiple tests of significance Biometrika 75 800–802
JH Hoeijmakers (2001) ArticleTitleGenome maintenance mechanisms for preventing cancer Nature 411 366–374 Occurrence Handle10.1038/35077232 Occurrence Handle1:CAS:528:DC%2BD3MXktVSjs74%3D Occurrence Handle11357144
IM Jones H Galick P Kato RG Langlois ML Mendelsohn GA Murphy P Pleshanov MJ Ramsey CB Thomas JD Tucker L Tureva I Vorobtsova DO Nelson (2002) ArticleTitleThree somatic genetic biomarkers and covariates in radiation-exposed Russian cleanup workers of the Chernobyl nuclear reactor 6–13 years after exposure Radiat Res 158 424–442 Occurrence Handle1:CAS:528:DC%2BD38XnslGnsb0%3D Occurrence Handle12236810
CM King ES Gillespic PG McKenna YA Barnett (1994) ArticleTitleAn investigation of mutation as a function of age in humans Mutat Res 316 79–90 Occurrence Handle1:CAS:528:DyaK2cXlslGqsb8%3D Occurrence Handle7521005
CM King HE Bristow-Craig ES Gillespie YA Barnett (1997) ArticleTitleIn vivo antioxidant status, DNA damage, mutation and DNA repair capacity in cultured lymphocytes from healthy 75- to 80-year-old humans Mutat Res 377 137–147 Occurrence Handle1:CAS:528:DyaK2sXjtlWls74%3D Occurrence Handle9219588
S Krichevsky G Pawelec A Gural RB Effros A Globerson DB Yehuda AB Yehuda (2004) ArticleTitleAge related microsatellite instability in T cells from healthy individuals Exp Gerontol 39 507–515 Occurrence Handle10.1016/j.exger.2003.12.016 Occurrence Handle1:CAS:528:DC%2BD2cXisF2nur8%3D Occurrence Handle15050284
SJ Lewis EJ Brunner (2004) ArticleTitleMethodological problems in genetic association studies of longevity – the apolipoprotein E gene as an example Int J Epidemiol 33 962–970 Occurrence Handle15319409
JN Lucas W Deng D Moore F Hill M Wade A Lewis F Sailes C Kramer A Hsieh N Galvan (1999) ArticleTitleBackground ionizing radiation plays a minor role in the production of chromosome translocations in a control population Int J Radiat Biol 75 819–827 Occurrence Handle10.1080/095530099139575 Occurrence Handle1:CAS:528:DyaK1MXkslGiurw%3D Occurrence Handle10489893
RM Lunn RG Langlois LL Hsieh CL Thompson DA Bell (1999) ArticleTitleXRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency Cancer Res 59 2557–2561 Occurrence Handle1:CAS:528:DyaK1MXjs1ymsLk%3D Occurrence Handle10363972
LJ Marnett (2000) ArticleTitleOxyradicals and DNA damage Carcinogenesis 21 361–370 Occurrence Handle10.1093/carcin/21.3.361 Occurrence Handle1:CAS:528:DC%2BD3cXitVeju7c%3D Occurrence Handle10688856
LJ Marnett JP Plastaras (2001) ArticleTitleEndogenous DNA damage and mutation Trends Genet 17 214–221 Occurrence Handle10.1016/S0168-9525(01)02239-9 Occurrence Handle1:CAS:528:DC%2BD3MXit1WnsL4%3D Occurrence Handle11275327
HW Mohrenweiser DM Wilson IM Jones (2003) ArticleTitleChallenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes Mutat Res 526 93–125 Occurrence Handle1:CAS:528:DC%2BD3sXjtFWqsr4%3D Occurrence Handle12714187
A Morley (1998) ArticleTitleSomatic mutation and ageing Ann NY Acad Sci 854 20–22 Occurrence Handle1:STN:280:DyaK1M7islektQ%3D%3D Occurrence Handle9928416
ML Muiras M Muller F Schachter A Burkle (1998) ArticleTitleIncreased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians J Mol Med 76 346–354 Occurrence Handle10.1007/s001090050226 Occurrence Handle1:CAS:528:DyaK1cXjtFaksrg%3D Occurrence Handle9587069
S Neri L Cattini A Facchini G Pawelec E Mariani (2004) ArticleTitleMicrosatellite instability in in vitro ageing of T lymphocyte clones Exp Gerontol 39 499–505 Occurrence Handle10.1016/j.exger.2003.11.017 Occurrence Handle1:CAS:528:DC%2BD2cXisF2nur4%3D Occurrence Handle15050283
B Pesch R Dusing S Rabstein V Harth D Grentrup T Bruning O Landt H Vetter YD Ko (2004) ArticleTitlePolymorphic metabolic susceptibility genes and longevity: a study in octogenarians Toxicol Lett 151 283–290 Occurrence Handle1:CAS:528:DC%2BD2cXks1WntLs%3D Occurrence Handle15177664
EA Price SL Bourne R Radbourne PA Lawton J Lamerdin LH Thompson JE Arrand (1997) ArticleTitleRare microsatellite polymorphisms in the DNA repair genes XRCC1, XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity Somat Cell Mol Genet 23 237–247 Occurrence Handle1:CAS:528:DyaK1cXitVOhtrs%3D Occurrence Handle9542526
MJ Ramsey DH Moore JF Briner DA Lee L Olsen JR Senft JD Tucker (1995) ArticleTitleThe effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting Mutat Res 338 95–106 Occurrence Handle1:CAS:528:DyaK2MXotFCrtLc%3D Occurrence Handle7565886
CL Relton CP Daniel DM Hammal L Parker EJ Tawn J Burn (2004) ArticleTitleDNA repair gene polymorphisms, pre-natal factors and the frequency of somatic mutations in the glycophorin-A gene among healthy newborns Mutat Res 545 49–57 Occurrence Handle1:CAS:528:DC%2BD3sXpvF2rtrs%3D Occurrence Handle14698416
CC Ruttan BW Glickman (2002) ArticleTitleCoding variants in human double-strand break DNA repair genes Mutat Res 509 175–200 Occurrence Handle1:CAS:528:DC%2BD38XosFCktL0%3D Occurrence Handle12427538
S Savas DY Kim MF Ahmad M Shariff H Ozcelik (2004) ArticleTitleIdentifying functional genetic variants in DNA repair pathway using protein conservation analysis Cancer Epidemiol Biomarkers Prev 13 801–807 Occurrence Handle1:CAS:528:DC%2BD2cXkt1GhtL8%3D Occurrence Handle15159313
MR Shen IM Jones H Mohrenweiser (1998) ArticleTitleNonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans Cancer Res 58 604–608 Occurrence Handle1:CAS:528:DyaK1cXht1antLo%3D Occurrence Handle9485007
G Slupphaug B Kavli HE Krokan (2003) ArticleTitleThe interacting pathways for prevention and repair of oxidative DNA damage Mutat Res 531 231–251 Occurrence Handle1:CAS:528:DC%2BD3sXpt1ertLw%3D Occurrence Handle14637258
E Taioli D Mari C Franceschi M Bonafe D Monti S Bertolini D Marinelli S Garte (2001) ArticleTitlePolymorphisms of drug-metabolizing enzymes in healthy nonagenarians and centenarians: difference at GSTT1 locus Biochem Biophys Res Commun 280 1389–1392 Occurrence Handle10.1006/bbrc.2001.4280 Occurrence Handle1:CAS:528:DC%2BD3MXptlCqsA%3D%3D Occurrence Handle11162685
T Takanami J Nakamura Y Kubota S Horiuchi (2005) ArticleTitleThe Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability Mutat Res 582 135–145 Occurrence Handle1:CAS:528:DC%2BD2MXitlChurc%3D Occurrence Handle15781218
EJ Tawn CA Whitehouse RE Tarone (2004) ArticleTitleFISH chromosome aberration analysis on retired radiation workers from the Sellafield nuclear facility Radiat Res 162 249–256 Occurrence Handle1:CAS:528:DC%2BD2cXns1yisLc%3D Occurrence Handle15378837
J Vijg (2000) ArticleTitleSomatic mutations and aging: a re-evaluation Mutat Res 447 117–135 Occurrence Handle1:CAS:528:DC%2BD3cXht1Ohsro%3D Occurrence Handle10686308
Y Wang MR Spitz Y Zhu Q Dong S Shete X Wu (2003) ArticleTitleFrom genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity DNA Repair 2 901–908 Occurrence Handle1:CAS:528:DC%2BD3sXlvVSgt7g%3D Occurrence Handle12893086
CA Whitehouse AA Edwards EJ Tawn G Stephan U Oestreicher JE Moquet DC Lloyd L Roy P Voisin C Lindholm J Barquinero L Barrios MR Caballin F Darroudi J Fomina (2005) ArticleTitleTranslocation yields in peripheral blood lymphocytes from control populations Int J Radiat Biol 81 139–145 Occurrence Handle1:CAS:528:DC%2BD2MXkslSrurc%3D Occurrence Handle16019923
CS Wilding CL Relton GS Rees RE Tarone CA Whitehouse EJ Tawn (2005) ArticleTitleDNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers Mutat Res 570 137–145 Occurrence Handle1:CAS:528:DC%2BD2MXosVOnuw%3D%3D Occurrence Handle15680411
G Zhu DL Duffy DR Turner KR Ewen GW Montgomery NG Martin (2003) ArticleTitleLinkage and association analysis of radiation damage repair genes XRCC3 and XRCC5 with-nevus density in adolescent twins Twin Res 6 315–321 Occurrence Handle10.1375/136905203322296683 Occurrence Handle14511439
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Wilding, C.S., Rees, G.S., Relton, C.L. et al. Genotype Profiles of Loci Encoding DNA Repair Enzymes in Newborn and Elderly Populations: No Evidence of Association with Longevity. Biogerontology 7, 35–41 (2006). https://doi.org/10.1007/s10522-005-6042-1
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DOI: https://doi.org/10.1007/s10522-005-6042-1